Real-world cross-comparison of metabolic outcomes with different sodium-glucose co-transporter 2 inhibitors agents in adults with type 2 diabetes: results from the Association of British Clinical Diabetologists audit programme

Abstract

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have demonstrated significant efficacy in improving cardiorenal and metabolic outcomes, However, whether there are differences between agents remain unclear. We therefore assessed changes in haemoglobin A1c (HbA1c), weight, body mass index (BMI) and systolic blood pressure (SBP) across the class; and between agents. Methods: Individuals using empagliflozin (E), canagliflozin (C) or dapagliflozin (D) in the ABCD audits were included provided that data were available for the outcomes of interest. Multivariate linear regression analysis was used to assess adjusted change in HbA1c, weight, BMI and SBP and to compare outcomes between drugs. Analyses were performed in Stata 17. Results: 21,263 individuals (E=11,231; C=2,257; D=7,775) with mean±SD age 60.0±10.4years, HbA1c 75.3±17.2 mmol/mol, BMI 33.9±7.1kg/m2 and 61.2% female were included. Over median follow-up of 1.7 years, HbA1c reduced by 10.0 mmol/mol (95% CI 9.8-10.2; p<0.001); weight reduced by 3.2 kg (95% CI 2.2-4.1; p<0.001); BMI reduced by 1.1 kg/m2 (95% CI 0.8-1.5; p<0.001) and SBP reduced by 0.9 mmHg (95% CI 0.7-1.1; p<0.001). Empagliflozin was associated with larger HbA1c reduction than dapagliflozin and canagliflozin (-10.6 mmol/mol [E] vs -9.8 mmol/mol [C] vs -9.1 mmol/mol [D]; p<0.001 for both). Canagliflozin was associated with statistically larger SBP reductions compared to dapagliflozin (-1.6 mmHg [C] vs 0.6 mmHg [D]). No differences were noted in weight and BMI change between drugs. Discontinuation of SGLT2i therapy was rare, only occurring in 0.35% (75/21,338). Our cohort has individuals with higher baseline weight and HbA1c compared to published trial data and may be more generalisable to a UK population. Conclusion: SGLT2i are very well tolerated and are associated with improvements in multiple metabolic and clinical parameters in UK real-world practice. Relatively small differences were observed between agents for HbA1c and SBP reduction, but not for weight reduction. Further work should focus on establishing the association between individual SGLT2i agents and hard cardiorenal end points in the real world.